The main thrust of this research is to explore the structure of antigenic determinants on the influenza viral hemagglutinin (HA) protein recognized by mouse cytolytic T lymphocytes (CTL) and other immune cells. Peptides from different regions of the HA will be synthesized chemically and will be tested for the ability to stimulate CTL, interleukin 2 producing helper T cells, and other proliferative T cells in vitro. The same antigens will also be tested for the ability to induce antibody formation in vivo. Peptides from corresponding regions of the HA from different influenza strains will be tested using a variety of congenic responder mice differing only in the H-2 region. The experiments will be designed to answer questions concerning the nature of the H-2-restricted recognition by CTL, the differences in antigenic determinants recognized by antibody-forming cells and different subclasses of T cells, the basis of genetic nonresponsiveness to different antigenic determinants in different mice, and differences in the frequencies of precursors for different types of T cells responding to different antigens in the spleen cells of both immunized and naive mice. Other experiments are intended to study if genetic nonresponsiveness of certain mice in mounting a CTL response to viruses is based in tolerance to self antigens. For these experiments, the hemagglutinin-neuraminidase of Sendai virus might be the system of choice; the main comparison will be between allorestricted and selfrestricted CTL. Experiments are also designed to place hydrophobic anchors such as fatty acids, perhaps with an amino acid spacer region, onto CTL stimulatory peptides to see if these peptides can be introduced onto the surfaces of peptide-free cells to sensitize the cells to lysis by peptide-specific CTL. (HF)